Previous work in this laboratory by Dr. Reichle and colleagues, has shown that rats with a portacaval shunt have a significantly lower incidence of mammary tumors after dimethylbenz (a) anthracene DMBA treatment, whether the shunt was constructed before or two weeks after treatment with DMBA. This proposal is concerned with investigating the possible involvement of metabolic and immunological factors in the anti- tumor effect of portacaval shunt in rats treated with a tumor-inducing dose of DMBA and to investigate the possible anti-tumor effect of a portacaval shunt in two other tumor systems; hepatomas induced by feeding rats 4-dimethy-amino-3-methylazobenzene and transplantable hepatomas (in collaboration with Dr. Harold Morris, Howard University). Metabolic studies will consist of: (1) qualitative studies of the types of metabolites formed from DMBA by homogenates of liver from rats which do or do not have a portacaval shunt and which have or have not been pretreated with DMBA, and (2) quantitative studies on the rate of hydroxylation of benzo (a) pyrene by homogenates of liver from groups of rats similar to those used in (1). To determine whether tumor resistance is due to immunologic factors, rats with and without a shunt will be treated with DMBA. Biopsied tumor and liver (retained tumor antigen) tissue will be injected intradermally into the shaved back of the autologous host to see if a skin reaction can be detected. After these animals are sacrificed, tumors and livers will be obtained and extracted. Sera from these animals will be tested for precipitating antibodies against autologous tumor and liver extracts, using a double diffusion-in-gel method. Similar immunologic studies will be conducted with rats that have received transplants of a Morris Hepatoma. The results of these experiments may provide insight into the mechanism of host resistance to a tumor and may suggest new avenues of chemotherapy or immunotherapy in cancer.